Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery

NEUROPHARMACOLOGY

卷:134

Review

Li, Peiying^1,2,3  Stetler, R. Anne^1,2  Leak, Rehana K.⁴  Shi, Yejie^1,2  Li, Yan³  Yu, Weifeng³  Bennett, Michael V. L.⁵  Chen, Jun^1,2 

[1] Univ Pittsburgh, Sch Med, Pittsburgh Inst Brain Disorders & Recovery, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA

[3] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Anesthesiol, Shanghai 200127, Peoples R China

[4] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA

[5] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA

关键词: Cerebral ischemia;    Oxidative stress;    DNA damage;    DNA repair;    Stroke recovery;    Neurovascular remodeling;    White matter repair;    Axonal regeneration;    Neurogenesis;   

DOI  :  10.1016/j.neuropharm.2017.11.011

来源: Elsevier

【 摘 要 】

The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ). Defective DNA repair is tightly correlated with worse neurological outcomes after stroke, whereas upregulation of DNA repair enzymes, such as APE1, OGG1, and XRCC1, improves long-term functional recovery following stroke. Indeed, DNA damage and repair are now known to play critical roles in fundamental aspects of stroke recovery, such as neurogenesis, white matter recovery, and neurovascular unit remodeling. Several DNA repair enzymes are essential for comprehensive neural repair mechanisms after stroke, including Pol beta and NEIL3 for neurogenesis, APEI for white matter repair, Gadd45b for axonal regeneration, and DNA-PKs for neurovascular remodeling. This review discusses the emerging role of DNA damage and repair in functional recovery after stroke and highlights the contribution of DNA repair to regenerative elements after stroke. This article is part of the Special Issue entitled 'Cerebral Ischemia'. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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